Oligodendrogliomas (ODs) account for 20% of brain tumors in adults and, as their name suggests, they have prominent oligodendroglial differentiation (1, 2). These tumors generally arise in the white matter of cerebral hemispheres, in the frontal lobes. Well-differentiated ODs can evolve into high-grade “anaplastic” ODs, though it is often difficult to clearly distinguish these two types from each other or from other brain tumors (1, 2). Because this distinction is important for the management of patients, molecular biomarkers for ODs are of great interest.
To date, the best biomarker for ODs is loss of heterozygosity (LOH) of chromsomes 1p and 19q (2-5). Assessment for LOH events is now commonly performed in patients with ODs because of their important implications for therapeutic responses (2-5). The chromosome losses occur in 50% to 70% of tumors and are often associated with a pericentromeric translocation of chromosomes 1 and 19, producing marker chromosome der(1;19) (q10;p10) (2-7). This translocation is unbalanced, leaving the cells with one copy of the short arm of chromosome 1 and one copy of the long arm of chromosome 19. The functional basis for most cancer translocations involves one of the genes residing near the breakpoints, producing fusions that alter the gene's product. In contrast, the der(1;19) (q10;p10) breakpoints are in gene-poor centromeric regions and are always associated with LOH (4, 6, 8). This suggests that the basis for the t(1;19) translocation is the unmasking of a tumor suppressor gene(s) on either chromosome 1p or 19q (2-5), (9). This is supported by the fact that some tumors lose only chromosome 1p sequences, while others lose only chromosome 19q sequences.
There is a continuing need in the art to identify this putative tumor suppressor gene(s), as well as to increase understanding of OD pathogenesis.